Sorry, that note to "Janet" in the middle of the post, was from me to my
daughter who does basic ( very basic ) medical research. I just put the wrong
address on it. Nita

Flemco- wrote:

> The point is Novartis spent nearly $1Billion on this technology.
> Dramatically more than the pittance the US government is proposing and we
> keep drooling over.  Let's face it.  If you want anything done, the
> government is not the place to look.
>
> Larry Fleming
> 54/51
> [log in to unmask]
> http://homepages.msn.com/HobbyCt/flemco
>
> -----Original Message-----
> From:   Parkinson's Information Exchange Network
> [mailto:[log in to unmask]] On Behalf Of Nita Andres
> Sent:   Thursday, October 28, 1999 1:57 PM
> To:     [log in to unmask]
> Subject:        Re: Gene Therapy
>
> Janet, more on Novartis and gene therapy. How much time do drug companies
> spend
> on developing drugs before they throw in the towel?  Really strange, it
> seems to
> me that it would take a lot of time. Love, Mother
>
> Flemco- wrote:
>
> > Researchers Get Dose of Reality
> > As Logistics Stymie Gene Therapy
> > By ROBERT LANGRETH and STEPHEN D. MOORE
> > Staff Reporters of THE WALL STREET JOURNAL
> > Eight years ago, Swiss drug maker Sandoz AG was dazzled by a tiny U.S.
> > biotechnology firm doing promising work in the new field of gene therapy.
> > Genetic Therapy Inc. and government scientist French Anderson, its
> > co-founder, claimed that injecting healthy genes into the body to replace
> > damaged or defective ones would revolutionize medicine by letting doctors
> > attack the causes of diseases such as cancer and cystic fibrosis, rather
> > than just the symptoms.
> > Sandoz, which would merge with Swiss rival Ciba-Geigy AG in 1996 to form
> > Novartis AG, bought into this bold new vision. It began amassing GTI
> shares
> > in 1991; in 1995, it bought the Gaithersburg, Md., company outright,
> > bringing its total investment in GTI to more than $300 million. By 1997,
> > Sandoz, looking for new technologies to fuel its profits, also had
> invested
> > $548 million to acquire SyStemix Inc., which was developing a related
> > process.
> > These days, however, gene therapy looks unlikely to pay off in a big way
> > anytime soon. And Novartis is scrambling to salvage its nearly $1 billion
> > investment in the technology. All but one of the human gene-therapy
> testing
> > programs once under way at GTI and SyStemix have been scrapped or
> > temporarily halted. And none of the hundreds of human studies conducted
> > elsewhere around the globe so far have offered clear proof that gene
> therapy
> > works in any significant way to fight disease.
> > "This has been an overhyped area that has failed to reach its promise for
> > very obvious technical reasons," says George Poste, a top research
> executive
> > at British pharmaceutical maker SmithKline Beecham PLC.
> > 'We Were Naive'
> > Even Dr. Anderson has tempered his enthusiasm. "We were naive to think we
> > could revolutionize medicine in 10 years," says the researcher, who now
> > doubts that major gene-therapy drugs will reach the market before 2004 or
> > 2005.
> > Indeed, the sudden death last month of a patient undergoing experimental
> > treatment for a rare liver disorder at the University of Pennsylvania --
> the
> > first death apparently linked to gene therapy -- has raised questions
> about
> > whether scientists have been in too big a hurry to test such therapy on
> > humans. As a precaution, federal regulators since have ordered U.S. drug
> > maker Schering-Plough Corp., which wasn't involved in the University of
> > Pennsylvania research project, to temporarily stop enrolling new patients
> in
> > certain gene-therapy trials for cancer.
> > Back in 1990, though, gene therapy was generating enormous excitement. Dr.
> > Anderson and his colleagues at the National Institutes of Health treated a
> > young girl with a rare and potentially fatal immune disorder called ADA
> > deficiency, or "boy-in-the-bubble" disease. Dozens of hospitals and
> medical
> > schools sought government approval for human trials for other illnesses.
> > Boosters went so far as to predict that the first gene therapies would hit
> > the market as early as 1996.
> > Sandoz, one of the pharmaceutical industry's most aggressive investors in
> > the new field, had high hopes of using gene therapy to treat the deadliest
> > form of brain cancer, glioblastoma, and other cancers. But in 1998,
> Novartis
> > quietly abandoned its flagship gene-therapy project after a large-scale
> > human test failed to prove that the therapy was effective. And, earlier
> this
> > year, the drug maker undertook a painful overhaul of its entire
> gene-therapy
> > research program. Now, Michael Perry, who has run both GTI and SyStemix
> > since their operations were combined last fall, says no new human tests
> are
> > planned until a host of technical issues are resolved.
> > A Crucial 24 Months
> > "Novartis is not proud of it right now," Dr. Anderson says of the program.
> > "Something has got to show up on the radar screen in the next 24 months or
> > some really serious decisions are going to be made" says the researcher,
> who
> > serves on GTI's board and is now a University of Southern California
> medical
> > school professor.
> > Even so, Novartis Chief Executive Daniel Vasella says his company remains
> > committed to the field. "There isn't a single major drug on the market
> that
> > hasn't been close to the grave at some point," he says. If gene therapy
> > ultimately fails to produce a major product, "I'd still say fair enough.
> > That's our business. If you don't spend big money and take big risks, you
> > shouldn't be in the pharmaceutical industry," adds Mr. Vasella, who notes
> > that gene therapy accounts for a small fraction of Novartis's annual
> > health-care research budget of more than $2 billion.
> > >From the beginning, the therapy's main difficulty has been a logistical
> one:
> > how to deliver enough healthy genes to the appropriate site and get them
> to
> > stay there long enough to cure or alleviate a disease. For example,
> > researchers estimate that to cure cystic fibrosis, a hereditary
> respiratory
> > disorder, new genes would have to be permanently placed in a billion
> > defective cells in the lung's airways. Researchers often use genetically
> > engineered viruses as vehicles for such genes. For example, an adenovirus
> > was used as the carrier in the University of Pennsylvania trial in which
> the
> > patient died. But the technique has its drawbacks: Sometimes a patient's
> > immune system, wary of foreign invaders, tries to fight off the viral
> > vehicles. To be sure, gene-therapy researchers recently have made progress
> > in some areas, such as treating heart disease or hemophilia. But overall,
> > the therapy's short-term applications seem narrower than they did a few
> > years ago.
> > Confident of a Breakthrough
> > After Sandoz and GTI began working together in November 1991, GTI
> scientists
> > were confident of achieving a breakthrough. The feeling was: "We are going
> > to do something very important here," says Alan McClelland, a former GTI
> > research manager now at rival Avigen Inc.
> > GTI's showcase gene-therapy effort, aimed at treating glioblastoma, was
> > conceived by colleagues of Dr. Anderson at NIH. It involved inserting
> > so-called suicide genes into the DNA of tumor cells to make them sensitive
> > to the antiviral drug ganciclovir; doctors could then give patients the
> > antiviral to kill the tumor cells.
> > The first human test was conducted in the early 1990s at the NIH, with GTI
> > as a partner. Initial results seemed highly encouraging. The first
> patient's
> > tumor shrank dramatically following the treatment. Although distant tumors
> > eventually killed him eight months later, the original tumor never came
> > back. A second patient showed no response. A third patient's tumor also
> > shrank significantly, though only temporarily. Overall, the tumors of six
> of
> > the 15 patients studied showed some shrinking in response to the therapy;
> in
> > one case, the tumor disappeared entirely and the patient seemed to fully
> > recover, a rare outcome in glioblastoma.
> > GTI executives didn't wait for all the data to come in before they began
> > planning a second test on a few dozen patients at the University of
> > Washington and elsewhere. But even as these new tests were launched,
> Edward
> > Oldfield, an NIH neurosurgeon, was analyzing the results of the first
> trial,
> > which he had led, and he was growing increasingly skeptical of the
> therapy.
> > It seemed the new genes penetrated only a tiny fraction of tumor cells in
> > the immediate vicinity of the injection. While this killed nearby cancer
> > cells, a phenomenon dubbed "the bystander effect," it seemed to have no
> > impact on cells farther afield. And Dr. Oldfield wasn't convinced that the
> > one patient's recovery was fully a result of the gene treatment.
> > "We didn't think it had enough activity to be meaningful. Based on what we
> > had seen, I saw no hope of distributing the gene where it needed to go,"
> > says Dr. Oldfield, a surgical chief at the National Institute of
> > Neurological Diseases and Stroke.
> > By 1994, Sandoz had decided to expand its collaboration with GTI to
> include
> > the glioblastoma work. It started its own small human test in Europe. The
> > initial results were mixed, and oncologist Athos Gianella-Borradori, the
> > Sandoz official helping coordinate the trial, says he had doubts the
> > treatment would work. He says he told his superiors at Sandoz and
> officials
> > at GTI of his reservations, aware they might be interpreted "as a betrayal
> > of our cause."
> > He had another concern: By late 1995, several prominent gene-therapy
> trials
> > elsewhere had failed, leading some to question the validity of the entire
> > approach. Dr. Gianella-Borradori, who left Sandoz a few years ago and now
> > works at Bavarian Nordic GmbH in Germany, says he didn't want another such
> > failure.
> > That same year, an NIH committee set up to review gene therapy concluded
> > that problems remained "in all basic aspects" of the technology. Top
> > researchers were reporting disappointing results. Scientists at the
> > University of North Carolina in Chapel Hill disclosed that a trial for
> > cystic fibrosis produced side effects and didn't alleviate the disease.
> > Another trial, at Ohio State University, found that a muscular-dystrophy
> > treatment didn't improve muscle strength.
> > Still, GTI and Sandoz forged ahead. Although gene therapy affected only a
> > limited number of cancer cells directly in the glioblastoma project,
> Sandoz
> > was impressed by the fact that a handful of patients in the various trials
> > appeared to be among the rare long-term survivors of the disease.
> > Researchers theorized that the new genes had triggered an immune response
> > against the cancer. A neurosurgeon who led the University of Washington
> > trial says he was so taken by his results that he flew to Switzerland, to
> > urge Sandoz to continue the program.
> > Comparative Study
> > In 1996, Sandoz, soon to become Novartis, launched a large trial that
> would
> > compare the effectiveness of gene therapy combined with standard treatment
> > to that of standard treatment alone. It would be by far the largest
> > gene-therapy trial to date, with more than 200 patients.
> > Novartis development chief Joerg Reinhardt says the company was fully
> aware
> > of the high risk of failure. But given the reports of patients who seemed
> to
> > respond to treatment, Novartis felt larger brain-cancer trials were in
> > order. The test began in the summer of 1996 at hospitals in Europe and the
> > U.S.
> > Meanwhile, GTI's gene-therapy treatments for other diseases were running
> > into problems. When Sandoz bought it out in August 1995, GTI was involved
> in
> > early-stage human tests of therapies for cystic fibrosis, breast cancer
> and
> > several rare genetic diseases. But these efforts were halted, one by one,
> as
> > it became clear that existing gene-delivery technology couldn't deliver
> > enough genes to do the job. Novartis says Sandoz wasn't counting on any of
> > these preliminary tests to succeed when it bought GTI.
> > Different Concepts of Time
> > As project after project stumbled, Novartis grew worried that GTI's
> approach
> > was too scattered. There were "too many things going on, and not enough
> > focus," says Paul Herrling, Novartis's research director. Novartis
> attempted
> > to impress its deliberate decision-making style on GTI, but ended up
> > frustrating some researchers there. A running joke was that at GTI the
> clock
> > ticked in days, but at Novartis it ticked in quarters. Dr. Herrling says
> > there were clashes. "We had no experience with this biotechnology; they
> had
> > no experience with drug development."
> > In another setback, the U.S. Federal Trade Commission, reviewing the
> > proposed Sandoz-Ciba merger in 1996, demanded -- as a condition for
> > approving the deal -- that rights to key GTI patents be offered to rival
> > companies. Sales of gene-therapy drugs, the FTC predicted, could reach $45
> > billion a year by 2010 -- a figure that today seems highly unrealistic.
> > By early 1998, preliminary results of the large-scale comparative trials
> on
> > brain-cancer patients were rolling in. They didn't look good. Patients who
> > underwent gene therapy didn't live longer than those receiving standard
> > treatment. For Novartis, it was the final straw.
> > Returning a Verdict
> > In mid-1998, the panel of scientists that reviews Novartis's research each
> > year took a hard look at gene therapy. Its verdict: Improved gene-delivery
> > methods were needed in order to give human tests a better chance of
> success.
> > Soon thereafter, Novartis combined GTI and SyStemix. Many GTI officials
> were
> > shocked when GTI bore the brunt of the cuts, which included most of GTI's
> > senior managers for drug development. Roughly 90 employees, or about 20%
> of
> > the two units' combined staffs, were laid off, the vast majority of them
> at
> > GTI. Mr. Perry, a Novartis insider who had been running SyStemix for more
> > than a year, was chosen to head the combined operation from SyStemix's
> Palo
> > Alto, Calif., laboratory. The decision, Mr. Perry says, didn't reflect on
> > the quality of GTI's researchers.
> > Dr. Anderson sees it differently. GTI was "charging off in various
> > directions" and not always conforming to Novartis's corporate goals.
> > Novartis had tried to rein in the company, but "wasn't successful."
> > Novartis has since scaled back or eliminated many gene-therapy research
> > projects. "It is not on my high priority list to go into the clinic now,"
> > Mr. Perry says. But he says he is "positive" that gene therapy will play a
> > major role in medicine, and that Novartis's past experience will give it
> an
> > edge. "Certainly, there is pressure" to produce a return on Novartis's
> > investment, he says. "It is a question of when, not if."
> >
> > Larry Fleming
> > [log in to unmask]
> > http://homepages.msn.com/HobbyCt/flemco